Bacterial infections are treated with antibiotics; however, bacteria can develop antibiotic resistance, leading current researchers to explore alternative strategies. Spray-dried nanoparticle-in-microsphere formulations, made of aluminum oxide nanoparticles (Al₂O₃ NPs), zinc oxide (ZnO), zinc oxide NPs (ZnO NPs), and cellulose nanocrystals (CNCs), with effective antimicrobial and antibiofilm activity against Gram-negative and Gram-positive bacteria, are described. We validated that the antimicrobial properties of metal oxide nanoparticles-in-microspheres are higher than each of the raw materials used in any formulation tested, Figure 1. We verified the impact of the ratios in the components of the formulations on the antimicrobial properties and toxicity of metal oxide nanoparticles-in-microspheres. A formulation made of CNCs (weight % ≥ 0.75%) and an equal weight % of Al₂O₃ NPs and ZnO NPs (~ 0.25% per type of NPs) generated the highest antimicrobial and antibiofilm activity (Gram-positive bacteria (both methicillin-resistant Staphylococcus aureus (MRSA) USA300 LAC, and MRSA SAP0017) and Gram-negative bacteria, including Escherichia coli ATTC489, Pseudomonas aeruginosa, PAO1, and Acinetobacter baumannii ATTC5015), Figure 2. Moreover, the toxicity of these formulations, tested against peripheral blood mononuclear cells, was very minimal (≤500 µg/ml) and significantly lower than the toxicity of the metal oxide NPs when tested alone, Figure 2.

<b>Figure.1</b> <i>Impact of the formulation on the antimicrobial properties of spray-dried microspheres.</i>

Figure.1 Impact of the formulation on the antimicrobial properties of spray-dried microspheres.

<b>Figure.2</b> <i>Toxicology a) and b) and antimicrobial c) and antibiofilm d) of raw materials and metal oxide nanoparticles-in-microspheres.</i>

Figure.2 Toxicology a) and b) and antimicrobial c) and antibiofilm d) of raw materials and metal oxide nanoparticles-in-microspheres.

Feng Jiang

The University of British Columbia

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